Functional Specialization and Topographic Segregation of Hippocampal Astrocytes

Abstract

Astrocytes have been suggested to play several roles in the complex control of brain microenvironment. However, they have been generally considered to constitute a homogeneous population of cells. Here we show that at least three electrophysiologically distinct types of astrocytes can be found in the mature hippocampus. These subpopulations of glia were characterized by expression of different ion currents. In astrocytes exposed to elevated K ϩ , Cs ϩ prevented influx of K ϩ only in cells with inwardly rectifying currents (I IR ). The topographic distribution of glia with Cs ϩ -sensitive inward rectifying currents (involved in K ϩ buffering) was nonuniform. Cs ϩ -sensitive astrocytes were predominantly found in CA3 radiatum, whereas most CA1 astrocytes were Cs ϩ -insensitive. Functional significance of the spatial segregation of glial cells with inward rectification was addressed in slices that were bathed in Cs ϩ -containing media. Under these conditions, neuronal stimulation induced spontaneous epileptiform activity, which first appeared in CA3 and was then synaptically propagated to CA1. Intracellular labeling of astrocytes with biocytin revealed that CA1 astrocytes are characterized by a high degree of cell-to-cell coupling; in contrast, cell labeling in CA3 revealed smaller groups and occasionally individual cells. Three individual biocytin-labeled cells had electrophysiological properties indistinguishable from Cs ϩ -sensitive astrocytes but had morphology typical of oligodendroglia. These results provide evidence for a role of K ϩ uptake via I IR into astrocytes. The segregated expression of potassium channels in a subpopulation of astrocytes suggests that functionally specialized cell types are involved in K ϩ homeostasis.

What Non-neuronal Mechanisms Should Be Studied to Understand Epileptic Seizures?

“…In particular, they play a crucial role in the regulation of the concentration of potassium [73]. Glia express both aquaporins and potassium channels (inward rectifying and delayed rectifying) that play a role in this glial function through maintaining potassium and water homeostasis [5, 11, 18]. In addition, the connection of glia through gap junctions results in a glial syncytium, which facilitates not only water and potassium buffering but also glial communication [23].…”

Potassium diffusive coupling in neural networks

“…The role of axons in potassium homeostasis has been analysed from computational studies (Bellinger et al 2008a,b;Liu et al 2008), and is difficult to assess experimentally. Tse et al 1992;Sontheimer & Waxman 1993;Amedee et al 1997;D'Ambrosio et al 1998;Chvatal et al 1999). In addition, potassium channels are distributed not only in the dendrites and soma of CA1 pyramidal cells, but also are present along the axon (juxtaparanodal regions, Kv1.1, Kv1.2) and in its terminals (Mongilner et al 2001;Pedraza et al 2001;Devaux et al 2003).…”

Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity

“…These observations prompted a novel view on the physiological meaning of this tonic inhibition mediated by inhibitory A 1 receptors. In fact, astrocytes respond to neuronal activity with a time course considerably slower than neurons (tenths of seconds versus milliseconds; see Fellin et al, 2004) and promote broad volume transmission (reviewed in Halassa et al, 2007;Haydon and Carmignoto, 2006;Scemes and Giaume, 2006) thanks to their syncytium-like connectivity (D'Ambrosio et al, 1998;Latour et al, 2001;Wallraff et al, 2004) and to the number of synapses (near 10,000) contacted by each astrocyte (Bushong et al, 2003;Ventura and Harris, 1999). This means that astrocytic-derived adenosine can only be aimed at setting a global inhibitory tonus as a function of a timeaveraged activity in a broad neuronal circuit.…”